Understanding the High Longitudinal Relaxivity of Gd(DTPA)-Intercalated (Zn,Al)-Layered Double Hydroxide Nanoparticles

In this study, biocompatible gadolinium diethylenetriaminepentaacetate (Gd(DTPA))-intercalated (Zn,Al)-layered double hydroxide (LDH) nanoparticles were synthesized, characterized for Gd(DTPA) loading percentage and nanostructure, and the spin-lattice relaxation times (T₁) measured to determine their suitability as a potential T₁-weighted contrast agent for magnetic resonance imaging (MRI). Compared to the most commonly used contrast agent in clinical MRI (i.e., molecular Gd(DTPA)), significant increases in longitudinal relaxivity (r₁) were measured for all Gd(DTPA)-intercalated nanoparticles. For a specific Zn₂Al(OH)₆(Cl,0.5CO₃)_0.56Gd(DTPA)_0.086·xH₂O composition, r₁ was found to be 28.38 s^-1 mM^-1, which is over 6 times the r₁ of molecular Gd(DTPA). This dramatic increase in r₁ is attributed to (a) the much longer rotational correlation time (τ_R) of nanoparticles and (b) the inherent water of LDH that forms the second-/outer-sphere in the vicinity of intercalated Gd(DTPA)^2-. The latter, with an extensive hydrogen bonding network and insignificant translational motion, results in a longer mean residence lifetime (τ_M), which makes the contribution of second-/outer-sphere significant. Therefore, when the Gd(DTPA)^2- loading percentage increases from 8.6 to 55%, the diminution of the ratio of inherent water to Gd(DTPA)^2- concomitantly diminishes the contributions by second-/outer-sphere water to r₁. Additionally, the modest increase in r₁ with decreasing particle size (∼315-540 nm) is perhaps due to the shortening of τ_M. Finally, the spin-spin relaxation times (T₂) of ¹⁷O, determined at various temperatures, show a negligible exchange of water molecules at room temperature. Therefore, the very high r₁ of nanoparticles indicate that protons of the bulk water are still accessible to the Gd³⁺ centers, possibly dominated by prototropic exchange through the hydrogen bonding network.